| Abstract
| - Various approaches to the synthesis of all four stereoisomers of 2-(1H-imidazol-4-yl)cyclopropylamine (cyclopropylhistamine) are described. The rapid and convenient synthesis andresolution of trans-cyclopropylhistamine is reported. The absolute configuration of its enantiomers was determined by single-crystal X-ray crystallographic analysis. The distinct trans-cyclopropylhistamine enantiomers were tested for their activity and affinity on the histamineH3 receptor. (1S,2S)-Cyclopropylhistamine (VUF 5297) acts as an agonist both on the rat cortex(pD2 = 7.1; α = 0.75) and on guinea pig jejunum (pD2 = 6.6; α = 0.75). Its enantiomer, (1R,2R)-cyclopropylhistamine (VUF 5296), is about 1 order of magnitude less active. Both enantiomersshow weak activity on H1 and H2 receptors. All synthetic attempts to cis-cyclopropylhistaminewere unsuccessful. Nevertheless, the results of this study provide an ideal template formolecular modeling studies of histamine H3 receptor ligands.
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